Institut für Organische Chemie, Universität Regensburg , D-93053 Regensburg, Germany.
Institut für Organische Chemie, Universität Leipzig , D-04103 Leipzig, Germany.
J Am Chem Soc. 2016 Aug 10;138(31):9864-73. doi: 10.1021/jacs.6b04008. Epub 2016 Aug 2.
Catalysis with remote-stereocontrol provides special challenges in design and comprehension. One famous example is the dienamine catalysis, for which high ee values are reported despite insufficient shielding of the second double bond. Especially for dienamines with variable Z/E-ratios of the second double bond, no correlations to the ee values are found. Therefore, the structures, thermodynamics, and kinetics of dienamine intermediates in SN-type reactions are investigated. The NMR studies show that the preferred dienamine conformation provides an effective shielding if large electrophiles are used. Calculations at SCS-MP2/CBS-level of theory and experimental data of the dienamine formation show kinetic preference for the Z-isomer of the second double bond and a slow isomerization toward the thermodynamically preferred E-isomer. Modulations of the rate-determining step, by variation of the concentration of the electrophile, allow the conversion of dienamines to be observed. With electrophiles, a faster reaction of Z- than of E-isomers is observed experimentally. Calculations corroborate these results by correlating ee values of three catalysts with the kinetics of the electrophilic attack and reveal the significance of CH-π and stacking interactions in the transition states. Thus, for the first time a comprehensive understanding of the remote stereocontrol in γ-functionalization reactions of dienamines and an explanation to the "Z/E-dilemma" are presented. The combination of bulky catalyst subsystems and large electrophiles provides a shielding of one face and causes different reactivities of E/Z-dienamines in nucleophilic attacks from the other face. Kinetic preferences for the formation of Z-dienamines and their unfavorable thermodynamics support high ee values.
远程立体控制催化在设计和理解方面带来了特殊的挑战。一个著名的例子是烯胺催化，尽管第二个双键的屏蔽不足，但仍报告了高对映体过量值。特别是对于第二个双键的 Z/E-比例可变的烯胺，没有发现与对映体过量值相关的关系。因此，研究了 SN 型反应中烯胺中间体的结构、热力学和动力学。NMR 研究表明，如果使用大的亲电试剂，优选的烯胺构象提供了有效的屏蔽。SCS-MP2/CBS 理论水平的计算和烯胺形成的实验数据表明，第二个双键的 Z-异构体具有动力学优势，并且向热力学上更有利的 E-异构体的缓慢异构化。通过改变亲电试剂的浓度来调节速率决定步骤，允许观察烯胺的转化。实验中观察到亲电试剂与 Z-异构体的反应比 E-异构体快。计算通过将三个催化剂的对映体过量值与亲电攻击的动力学相关联，证实了这些结果，并揭示了 CH-π 和堆积相互作用在过渡态中的重要性。因此，首次全面了解了烯胺的γ-官能化反应中的远程立体控制，并解释了“Z/E 困境”。大的催化剂子系统和大的亲电试剂的组合提供了一个面的屏蔽，并导致亲核进攻时 E/Z-烯胺具有不同的反应性从另一面。Z-烯胺形成的动力学优势及其不利的热力学支持高对映体过量值。
